Structural biology of SARS-CoV-2 Mpro and drug discovery

Y Duan, H Wang, Z Yuan, H Yang - Current Opinion in Structural Biology, 2023 - Elsevier
Since its outbreak in late 2019, the COVID-19 pandemic has drawn enormous attention
worldwide as a consequence of being the most disastrous infectious disease in the past …

Preparing for the next viral threat with broad-spectrum antivirals

M Karim, CW Lo, S Einav - The Journal of Clinical …, 2023 - Am Soc Clin Investig
There is a large global unmet need for the development of countermeasures to combat
hundreds of viruses known to cause human disease and for the establishment of a …

Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir

Y Hu, EM Lewandowski, H Tan, X Zhang… - ACS Central …, 2023 - ACS Publications
The SARS-CoV-2 main protease (Mpro) is the drug target of Pfizer's oral drug nirmatrelvir.
The emergence of SARS-CoV-2 variants with mutations in Mpro raised the alarm of potential …

Nirmatrelvir-resistant SARS-CoV-2 variants with high fitness in an infectious cell culture system

Y Zhou, KA Gammeltoft, LA Ryberg, LV Pham… - Science …, 2022 - science.org
The oral protease inhibitor nirmatrelvir is of key importance for prevention of severe
coronavirus disease 2019 (COVID-19). To facilitate resistance monitoring, we studied …

Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors

SA Moghadasi, E Heilmann, AM Khalil, C Nnabuife… - Science …, 2023 - science.org
Vaccines and drugs have helped reduce disease severity and blunt the spread of severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, ongoing virus …

In vitro and in vivo characterization of SARS-CoV-2 resistance to ensitrelvir

M Kiso, S Yamayoshi, S Iida, Y Furusawa… - Nature …, 2023 - nature.com
Ensitrelvir, an oral antiviral agent that targets a SARS-CoV-2 main protease (3CLpro or
Nsp5), is clinically useful against SARS-CoV-2 including its omicron variants. Since most …

The Substitutions L50F, E166A, and L167F in SARS-CoV-2 3CLpro Are Selected by a Protease Inhibitor In Vitro and Confer Resistance To Nirmatrelvir

D Jochmans, C Liu, K Donckers, A Stoycheva… - MBio, 2023 - Am Soc Microbiol
The SARS-CoV-2 main protease (3CLpro) has an indispensable role in the viral life cycle
and is a therapeutic target for the treatment of COVID-19. The potential of 3CLpro-inhibitors …

In vitro and in vivo characterization of SARS-CoV-2 strains resistant to nirmatrelvir

M Kiso, Y Furusawa, R Uraki, M Imai… - Nature …, 2023 - nature.com
Nirmatrelvir, an oral antiviral agent that targets a SARS-CoV-2 main protease (3CLpro), is
clinically useful against infection with SARS-CoV-2 including its omicron variants. Since …

Global prevalence of SARS-CoV-2 3CL protease mutations associated with nirmatrelvir or ensitrelvir resistance

JD Ip, AWH Chu, WM Chan, RCY Leung… - …, 2023 - thelancet.com
Summary Background Nirmatrelvir-ritonavir (Paxlovid) and ensitrelvir are 3-chymotrypsin-
like cysteine protease (3CL pro) inhibitors which have been approved for the treatment of …

Comparing molnupiravir and nirmatrelvir/ritonavir efficacy and the effects on SARS-CoV-2 transmission in animal models

RM Cox, CM Lieber, JD Wolf, A Karimi… - Nature …, 2023 - nature.com
Therapeutic options against SARS-CoV-2 are underutilized. Two oral drugs, molnupiravir
and paxlovid (nirmatrelvir/ritonavir), have received emergency use authorization. Initial trials …